Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture

被引:163
作者
Kavanagh, KT
Hafer, LJ
Kim, DW
Mann, KK
Sherr, DH
Rogers, AE
Sonenshein, GE
机构
[1] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Program Res Womens Hlth, Boston, MA 02118 USA
[4] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA
关键词
green tea; breast cancer; EGCG; DMBA; p27(Kip1);
D O I
10.1002/jcb.1164
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epidemiological evidence suggests tea (Camellia sinensis L.) has chemopreventive effects against various tumors. Green tea contains many polyphenols, including epigallocatechin-3 gallate (EGCG), which possess antioxidant qualities. Reduction of chemically induced mammary gland carcinogenesis by green tea in a carcinogen-induced rat model has been suggested previously, but the results reported were not statistically significant. Here we have tested the effects of green tea on mammary tumorigenesis using the 7,12-dimethylbenz(a)anthracene (DMBA) Sprague-Dawley (S-D) rat model. We report that green tea significantly increased mean latency to first tumor, and reduced tumor burden and number of invasive tumors per tumor-bearing animal; although, it did not affect tumor number in the female rats. Furthermore, we show that proliferation and/or viability of cultured Hs578T and MDA-MB-231 estrogen receptor-negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA-transformed D3-1 cell line. Growth inhibition of Hs578T cells correlated with induction of p27(Kip1) cyclin-dependent kinase inhibitor (CKl) expression. Hs578T cells expressing elevated levels of p27(Kip1) protein due to stable ectopic expression displayed increased G1 arrest. Thus, green tea had significant chemopreventive effects on carcinogen-induced mammary tumorigenesis in female S-D rats. In culture, inhibition of human breast cancer cell proliferation by EGCG was mediated in part via induction of the p27(Kip1) CKl. (C) 2001 Wiley-Liss.
引用
收藏
页码:387 / 398
页数:12
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